Active Ingredients of Reduning Injection Maintain High Potency against SARS-CoV-2 Variants.

OBJECTIVE: To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin. METHODS: A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43. RESULTS: The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC50) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC50 lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43. CONCLUSIONS: The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.

Parametric study of anterior percutaneous endoscopic cervical discectomy (APECD).

Anterior percutaneous endoscopic cervical discectomy (APECD) is a common treatment for cervical spondylotic radiculopathy (CSR). In this study, the effects of various channel diameters and approach angles on cervical vertebrae on postoperative outcomes in APECD surgery were explored. A finite element model of intact cervical C3-C7 was constructed and then modified to obtain six surgical models. Range of motion (ROM) and intradiscal pressure (IDP) were calculated under different conditions of flexion (Fle), extension (Ext), lateral bending, and axial rotation. During Fle and bending to the left (LB), the ROM was closer to the intact model when the angle of approach was 90°. During bending to the left (LB) and rotation to the left (LR), the ROM changed considerably (43.2%, 33.7%, respectively) where the angle of approach was 45°. As the surgical channel diameter increased, the extent of the change in ROM compared with the intact model also increased. IDP decreased by 48% and 49%, respectively, compared with the intact model at the C5-C6 segment where the angle of approach was 45° and 60° during Fle, while it changed little at 90°, by less than 10%. The IDP was increased noticeably by 117.6%, 82.1%, and 105.8%, for channel diameters of 2, 3 and 4 mm, respectively. And declined noticeably during LB and LR (LB: 27.1%, 27.1%, 38.5%; LR: 37.4%, 35.5%, 48.7%). The results demonstrated that the shorter the surgical path, the smaller surgical diameter, the less the biomechanical influence on the cervical vertebra.

Does oblique lumbar interbody fusion promote adjacent degeneration in degenerative disc disease: A finite element analysis.

BACKGROUND: The number of oblique lumbar interbody fusion (OLIF) procedures has continued to rise over recent years. Adjacent segment degeneration (ASD) is a common complication following vertebral body fusion. Although the precise mechanism remains uncertain, ASD has gradually become more common in OLIF. Therefore, the present study analyzed the association between disc degeneration and OLIF to explore whether adjacent degeneration was promoted by OLIF in degenerative disc disease. METHODS: A three-dimensional nonlinear finite element (FE) model of the L3-S1 lumbar spine was developed and validated. Three lumbar spine degeneration models with different degrees of degeneration (mild, moderate and severe) and a model of OLIF surgery were constructed at the L4-L5 level. When subjected to a follower compressive load (500 N), hybrid moment loading was applied to all models of the lumbar spine and the range of motion (ROM), intradiscal pressure (IDP), facet joint force (FJF), average mises stress in the annulus (AMSA), average tresca stress in the annulus (ATSA) and average endplate stress (AES) were measured. RESULTS: Compared with the healthy lumbar spine model, the ROM, IDP, FJF, AMSA, ATSA and AES of the segments adjacent to the degenerated segment increased in each posture as the degree of disc degeneration increased. In different directions of motion, the ROM, IDP, FJF, AMSA, ATSA and AES in the OLIF model in the L3-L4 and L5-S1 segments were higher than those of the healthy model and each degenerated model. Compared with the healthy model, the largest relative increase in biomechanical parameters above (ROM, IDP, FJF, AMSA, ATSA or AES) was observed in the L3-L4 segment in the OLIF model, of 77.13%, 32.63%, 237.19%, 45.36%, 110.92% and 80.28%, respectively. In the L5-S1 segment the corresponding values were 68.88%, 36.12%, 147.24%, 46.00%, 45.88% and 51.29%, respectively. CONCLUSIONS: Both degenerated discs and OLIF surgery modified the pattern of motion and load distribution of adjacent segments (L3-L4 and L5-S1 segments). The increases in the biomechanical parameters of segments adjacent to the surgical segment in the OLIF model were more apparent than those of the degenerated models. In summary, OLIF risked accelerating the degeneration of segments adjacent to those of a surgical segment.

Application of Simulation Methods in Cervical Spine Dynamics.

Neck injury is one of the most frequent spine injuries due to the complex structure of the cervical spine. The high incidence of neck injuries in collision accidents can bring a heavy economic burden to the society. Therefore, knowing the potential mechanisms of cervical spine injury and dysfunction is significant for improving its prevention and treatment. The research on cervical spine dynamics mainly concerns the fields of automobile safety, aeronautics, and astronautics. Numerical simulation methods are beneficial to better understand the stresses and strains developed in soft tissues with investigators and have been roundly used in cervical biomechanics. In this article, the simulation methods for the development and application of cervical spine dynamic problems in the recent years have been reviewed. The study focused mainly on multibody and finite element models. The structure, material properties, and application fields, especially the whiplash injury, were analyzed in detail. It has been shown that simulation methods have made remarkable progress in the research of cervical dynamic injury mechanisms, and some suggestions on the research of cervical dynamics in the future have been proposed.

Biomechanical Effect of L4 -L5 Intervertebral Disc Degeneration on the Lower Lumbar Spine: A Finite Element Study.

OBJECTIVE: To ascertain the biomechanical effects of a degenerated L4 -L5 segment on the lower lumbar spine through a comprehensive simulation of disc degeneration. METHODS: A three-dimensional nonlinear finite element model of a normal L3 -S1 lumbar spine was constructed and validated. This normal model was then modified such that three degenerated models with different degrees of degeneration (mild, moderate, or severe) at the L4 -L5 level were constructed. While experiencing a follower compressive load (500 N), hybrid moment loads were applied to all models to determine range of motion (ROM), intradiscal pressure (IDP), maximum von Mises stress in the annulus, maximum shear stress in the annulus, and facet joint force. RESULTS: As the degree of disc degeneration increased, the ROM of the L4 -L5 degenerated segment declined dramatically in all postures (flexion: 5.79°-1.91°; extension: 5.53°-2.62°; right lateral bending: 4.47°-1.46°; left lateral bending: 4.86°-1.61°; right axial rotation: 2.69°-0.74°; left axial rotation: 2.69°-0.74°), while the ROM in adjacent segments increased (1.88°-8.19°). The largest percent decrease in motion of the L4 -L5 segment due to disc degeneration was in right axial rotation (75%), left axial rotation (69%), flexion (67%), right lateral bending (67%), left lateral bending right (67%), and extension (53%). The change in the trend of the IDP was the same as that of the ROM. Specifically, the IDP decreased (flexion: 0.592-0.09 MPa; extension: 0.678-0.334 MPa; right lateral bending: 0.498-0.205 MPa; left lateral bending: 0.523-0.272 MPa; right axial rotation: 0.535-0.246 MPa; left axial rotation: 0.53-0.266 MPa) in the L4 -L5 segment, while the IDP in adjacent segments increased (0.511-0.789 MPa). The maximum von Mises stress and maximum shear stress of the annulus in whole lumbar spine segments increased (L4 -L5 segment: 0.413-2.626 MPa and 0.412-2.783 MPa, respectively; adjacent segment of L4 -L5 : 0.356-1.493 MPa and 0.359-1.718 MPa, respectively) as degeneration of the disc progressively increased. There was no apparent regularity in facet joint force in the degenerated segment as the degree of disc degeneration increased. Nevertheless, facet joint forces in adjacent healthy segments increased as the degree of disc degeneration increased (extension: 49.7-295.3 N; lateral bending: 3.5-171.2 N; axial rotation: 140.2-258.8 N). CONCLUSION: Degenerated discs caused changes in the motion and loading pattern of the degenerated segments and adjacent normal segments. The abnormal load and motion in the degenerated models risked accelerating degeneration in the adjacent normal segments. In addition, accurate simulation of degenerated facet joints is essential for predicting changes in facet joint loads following disc degeneration.